Background: Breast cancer is the most relevant type of cancer and the second cause of cancer- related
deaths among women in general. Currently, there is no effective treatment for breast cancer although advances in its
initial diagnosis and treatment are available. Therefore, the value of novel anti-tumor therapeutic modalities remains
an immediate unmet need in clinical practice. Following our previous work regarding the properties of the Pluronics
with different photosensitizers (PS) for photodynamic therapy (PDT), in this study we aimed to evaluate the efficacy
of supersaturated hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) against breast cancer cells (MCF-7)
and non-tumorigenic breast cells (MCF-10A).
Methods: Cell internalization and subcellular distribution of HYP/P123 was confirmed by fluorescence microscopy.
The phototoxicity and citototoxicity of HYP/P123 was assessed by trypan blue exclusion assay in the presence and
absence of light. Long-term cytotoxicity was performed by clonogenic assay. Cell migration was determined by the
wound-healing assay. Apoptosis and necrosis assays were performed by annexin V-FITC/propidium Iodide (PI) by
Results: Our results showed that HYP/P123 micelles had high stability and high rates of binding to cells, which
resulted in the selective internalization in MCF-7, indicating their potential to permeate the membrane of these cells.
Moreover, HYP/P123 micelles accumulated in mitochondria and endoplasmic reticulum organelles, resulting in the
photodynamic cell death by necrosis. Additionally, HYP/P123 micelles showed effective and selective time- and
dose dependent phototoxic effects on MCF-7 cells but little damage to MCF-10A cells. HYP/P123 micelles inhibited
the generation of cellular colonies, indicating a possible capability to prevent the recurrence of breast cancer. We also
demonstrated that HYP/P123 micelles inhibit the migration of tumor cells, possibly by decreasing their ability to
Conclusion: Taken together, the results presented here indicate a potentially useful role of HYP/P123 micelles as a
platform for HYP delivery to more specifically and effectively treat human breast cancers through photodynamic
therapy, suggesting they are worthy for in vivo preclinical evaluations.